ACP issues guideline on glucose management for hospitalized patients

It's been almost a whole decade now that blood glucose management has been a cause
of turmoil and debate in hospital medicine. In November 2001, Van den Berghe and colleagues
published a study in the New England Journal of Medicine finding that intensive insulin therapy with glucose targets of 80 to 100 mg/dL reduced
morbidity and mortality in surgical intensive care unit (ICU) patients. Many hospitals
and hospitalists changed their management practices accordingly.

Then, in the late 2000s, other studies, including the NICE-SUGAR trial, began to provide
evidence that intensive insulin with a normoglycemic target harmed patients. Physicians,
hospitals and guidelines began shifting away from intensive control in light of the
emerging evidence against it, but questions and uncertainties remained.

In an effort to answer some of those questions, ACP experts recently gathered the
available evidence and developed a guideline regarding intensive insulin therapy for
general and ICU inpatients, published in the Feb. 15 Annals of Internal Medicine. Lead author Amir Qaseem, PhD, FACP, director of clinical policy for the College,
recently spoke to ACP Hospitalist about the guideline.

Q: Why were these guidelines needed?

A: Hyperglycemia is a very common finding among medical and surgical patients with or
without diabetes. It's associated with increased morbidity, mortality and cost, and
also poor immune response, increased cardiovascular events, thrombosis, etc. Most
clinicians make an effort to prevent and control this hyperglycemia in the inpatient
setting.

But what is the optimal target for the hospitalized patient in terms of glycemic control?
We wanted to address this issue. We address the management of hyperglycemia and evaluate
the benefits and harms associated with the use of intensive insulin therapy to achieve
tight glycemic control in hospitalized patients with or without diabetes.

Q: What are you seeing in current practice regarding inpatient glucose management?

A: The earlier trials that came out and strongly suggested that intensive insulin therapy
leads to better outcomes—it's something that has been widely adopted in hospitals
and in the ICU. But now there has been new evidence suggesting otherwise. This has
caused some confusion on what are the optimal targets. Is targeting normal glycemia
a good strategy or not a good strategy? Does it lead to better outcomes in patients
or not? In this paper, we define intensive insulin therapy as blood glucose between
80 and 110 mg/dL (4.4-6.1 mmol/L).

Q: Two of the new guideline's three recommendations tell physicians what not to do, rather
than specifying what glycemic levels they should target. Why is this?

A: You're right, some of the places we are saying what not to do because that's also
important. You can end up harming patients in doing certain things.

In the first recommendation, ACP recommends not using intensive insulin therapy to
strictly control blood glucose in non-surgical ICU/medical ICU [SICU/MICU] patients
with or without diabetes, which is a strong recommendation based on moderate-quality
evidence. What we found is that there is no reduction in mortality with the target
blood glucose levels between 80 and 180 mg/dL (4.4-10 mmol/L) compared to higher levels.
The [lower targets] did not have any impact in patients who had myocardial infarction,
stroke, brain injury or folks who are under perioperative care.

On the other hand, harms are likely to increase when target blood sugar levels are
too low. The reason we did not specify the target level is because in all these trials,
the range varied. However, we found that avoiding targets less than 140 mg/dL (7.8
mmol/L) definitely should be a priority, because that was leading to more harm. It
leads to hypoglycemia and increased length of stay and even increased mortality, although
the consequences of increased hypoglycemia were not really clear. Again, it goes back
to the [evidence being] so unclear. For non-SICU/MICU patients, we do not really specify
a target.

Q: How about the second and third recommendations?

A: For patients who are in the SICU and MICU, we recommend not using intensive insulin
therapy to normalize blood glucose in patients with or without diabetes. This is a
strong recommendation, based on high-quality evidence, because what we found is having
targets between 80 and 110 mg/dL (4.4-6.1 mmol/L), you're doing more damage than good.
It's associated with increase in mortality.

But what target level do you use in these patients? We recommend that between 140
and 200 mg/dL (7.8-10 mmol/L) is a reasonable target. That's a weak recommendation,
based on moderate-quality evidence. This is based on the levels utilized in the trials,
so that's all we can base our recommendation on. We do not have a precise and narrow
range for blood glucose level. What we found from the trials is if you keep the blood
glucose levels between 140 and 200 mg/dL (7.8-10 mmol/L), it's associated with similar
mortality outcomes as if you had it between 80 and 110 mg/dL (4.4-6.1 mmol/L).

Q: Is additional research needed to come to more definitive conclusions?

A: Yes, there's always more research that can be done. We probably can have more trials
on these insulin protocols in non-ICU settings. It's still not really clear what is
the impact of hypoglycemia or what specific target levels can be used in ICU settings
and non-ICU settings. More of these studies that can narrow down the range of the
target blood glucose level will always be helpful.

Q: The evidence and guidance on inpatient glucose management have varied widely in recent
years. Has the pendulum on this issue returned to a middle point where it's likely
to remain for some time?

A: This is all dependent on the evidence. In the past, the evidence showed that tight
glycemic control leads to better outcomes. But now we have enough evidence that shows
that tight glycemic control is actually doing more harm than benefit.

I always say our guidelines are based on current evidence. If some other high quality
trials came out that show something completely different, that may change something.
But I do think that tight glycemic control is definitely harmful. There is high quality
evidence that goes in that direction. But for now, this guideline is based on best
available current evidence.

Q: Any other advice you would offer hospitalists on this subject?

A: Intensive insulin therapy is associated with a high risk for severe hypoglycemia,
especially when the blood glucose level target is less than 6.7 mmol/L (120 mg/dL).
Given that the harms outweigh the benefits, we should not routinely implement strict
targets for blood glucose control in hospitalized patients.

A clinical practice guideline on use of intensive insulin therapy for the management
of glycemic control in hospitalized patients

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.